Chronic obstructive pulmonary disease (COPD, hereinafter), one of the representative lung diseases along with asthma, differs from asthma in that it accompanies an irreversible airway obstruction. COPD is an important disease which is currently ranked as the fourth leading cause of death in the world and shows a unique increase in its occurrence among the top ten diseases. COPD is a disease that occurs due to pathological changes in the bronchioles and lung parenchyma, which are caused by infections in the airway and lung parenchyma, and it is characterized by having obstructive bronchiolitis and emphysema (destruction of lung parenchyma). The types of COPD include chronic obstructive bronchitis, chronic bronchiolitis, and emphysema. The primary risk factor of COPD is thought to be cigarette smoking. Smoke acts as a strong toxic material in the lung tissue and causes promotion of the generation of oxidized materials, proinflammatory factors, and chemotactic factors, thereby promoting excessive transport of inflammatory cells such as neutrophils. The inflammatory cells transported to the inside of the lung tissue also secrete many inflammatory mediators, thus worsening the inflammation in the lung tissue. Examples of the well-known inflammatory mediators may include TNF-α, MIP-1, CXCL-1, etc., and they are used as important markers in inflammatory responses due to cigarette smoke.
The therapeutic materials used for treating COPD have been developed to improve the inflammation in the lung tissue, and they are mainly steroids, anti-inflammatory agents, etc. However, these therapeutic materials can cause various side-effects such as immunosuppression and resistance, and thus they are not suitable for the COPD patients who require long-term treatment.
Until now, in the case of COPD such as asthma, therapeutic agents having the effects of anti-inflammation or bronchodilation have mostly been used for the treatment of inflammation. However, a significant number of these conventional therapeutic agents require caution due to many side-effects. Examples of the representative therapeutic agents may include glucocorticoid, leukotriene modifiers, theophylline, etc. In the case of glucocorticoids, they have a strong effect but also have a problem in that they suppress all immune responses and anti-inflammatory responses including even the necessary immune responses instead of acting selectively, and thus there is an issue of drug side-effects and they are thus used for inhalation treatment. In the case of leukotriene modifiers, they have few side-effects but, due to the limited effects, they cannot control asthma when used alone, and thus they are mostly used as a subordinate agent. In the case of theophyllines, they have problems in that they do not have excellent effect and there is also a risk of side-effects. In the case of corticosteroids, they have an excellent therapeutic effect, but, under the long-term treatment, they are known to induce adrenal suppression, decrease of bone density, growth disorder, complications in the eyes and skin, increase of collagen synthesis, etc. in proportion to the dosage and duration of administration. In the case of long-acting β2 agonists such as salmeterol and formeterol, they exhibit a preventative effect against convulsions but they have been warned against because they may cause death of patients under certain conditions. Due to the various side-effects described above, the conventional therapeutic agents for treating inflammation require careful considerations in their use, and thus there is a need for the development of a therapeutic agent having an excellent effect with few side-effects. For this purpose, an accurate understanding of the mechanism of COPD is necessary.
Until now, the exact mechanism of COPD has been almost unknown, and there has been no therapeutic agent that can fundamentally treat the occurrence and progress of COPD, although various treatments have been attempted. Accordingly, studies on the pathogenesis of COPD and development of a fundamental therapeutic agent thereof based on the same are urgently required.
Nevertheless, a recent report related to the study of COPD revealed that chemotactic factors such as MIP-2 and CXCL-1, which promote the transport of inflammatory cells, have an important role in the occurrence and development of COPD (Lomas-Neira et al., 2005; Moriyama et al., 2010). In the progress of COPD, chemokines such as MIP-2 and CXCL-1 exhibit chemotactic effects via conjugation with the receptors of airway epithelial cells, pneumocytes, and inflammatory cells and induce an excessive infiltration of inflammatory cells into the inflammatory area in the lung tissue. Additionally, chemokines activate inflammatory cells, thereby producing proinflammatory factors such as TNF-α, IL-1β, IL-6, and IL-8. Specifically, in the case of TNF-α, it activates an inflammatory signaling system such as NF-κB and MAPK, thereby worsening the inflammatory responses. Additionally, chemokines not only produce proinflammatory factors but also produce various growth factors and reactive oxygen species, which cause sustained inflammation responses, damage in the lung parenchyma tissue, and fibrogenesis in the lung tissue (Lo et al., 2013). Due to a series of these reactions, deterioration in the pulmonary function, which is the most distinctive characteristic of COPD patients, is caused. Accordingly, the inhibition of chemokine production is thought to be a very important method for treating COPD. In fact, many researchers have made efforts to develop therapeutic materials for treating COPD with their studies being focused on the inhibition of chemokines (Buenestado et al., 2013).
Meanwhile, Pistacia weinmannifolia J. Poiss, Ex Franch is a plant widely cultivated near the Yunnan Province of China, and it has been used for treating shigellosis, gastroenteritis, flu, and headache since ancient times. According to a previous report, two compounds isolated from the plant were shown to have the ability to remove free oxygen radicals (Zhao X. et al., Biochim Biophys Acta, 1725, 103-110, 2005). However, except for the above report, the effect of Pistacia weinmannifolia extract, a fraction thereof, or a compound isolated therefrom with respect to the treatment or prevention of COPD has not been known.